REGULATION OF FERRITIN H-CHAIN EXPRESSION IN DIFFERENTIATING FRIEND-LEUKEMIA CELLS
REGULATION OF FERRITIN H-CHAIN EXPRESSION IN DIFFERENTIATING FRIEND-LEUKEMIA CELLS
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DOI：
10.1182/blood.v86.4.1570.bloodjournal8641570
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发表时间：
1995-08-15
期刊：
影响因子：
20.3
通讯作者：
BATTISTINI, A
中科院分区：
文献类型：
--
作者：
COCCIA, EM;STELLACCI, E;BATTISTINI, A
在Friend红白血病细胞（FLC）中研究了几种化合物诱导分化的铁蛋白（铁储存蛋白）表达的调节机制。在分化FLC中，施用氯化血红素使铁蛋白mRNA的稳态水平增加约15倍，铁蛋白含量增加约20至25倍。相反，铁盐对这些参数只有轻微的刺激作用，铁螯合剂对氯化血红素的刺激作用只有轻微的抑制作用。瞬时转染实验的构建体，其中人铁蛋白H-链启动子驱动的指示剂氯霉素乙酰转移酶（CAT）基因的表达表明，mRNA含量的增加主要是由于增强的转录。除了转录效应外，通过CAT试验显示，在mRNA铁蛋白铁响应元件的翻译控制下，用含有指示剂CAT mRNA编码区的构建体瞬时转染的细胞的翻译调节导致铁蛋白合成的进一步增加。我们的结论是，在诱导分化的FLC中，氯化血红素与分化诱导剂协同作用，增加铁蛋白表达。转录和翻译机制都是这种协同效应的原因。这似乎是分化的类红细胞的特征，因为在其它细胞类型（即成纤维细胞系）中未观察到。(C)1995年，美国血液学会。
The mechanisms that regulate the expression of ferritin, the iron storage protein, have been investigated in Friend erythroleukemia cells (FLCs) induced to differentiate by several chemical compounds. In differentiating FLCs, administration of hemin increases the steady-state level of ferritin mRNA about 15-fold and the ferritin content about 20- to 25-fold. Conversely, iron salts have only mild stimulatory effects on these parameters and iron chelators only slightly inhibited the stimulatory effect of hemin. Transient transfection experiments with a construct in which the human ferritin H-chain promoter drives the expression of the indicator chloramphenicol acetyltransferase (CAT) gene show that the increase in mRNA content is mainly due to enhanced transcription. In addition to transcriptional effects, translational regulation resulting in the further increase in ferritin synthesis is shown by CAT assays from cells transiently transfected with a construct containing the coding region for the indicator CAT mRNA under the translational control of the mRNA ferritin iron-responsive element. We conclude that, in FLCs induced to differentiate, hemin acts synergistically with the differentiation inducers, increasing ferritin expression. Both transcriptional and translational mechanisms are responsible for this synergistic effect. which appears to be characteristic of differentiated erythroid cells because it is not observed in other cell types (ie, fibroblastic cell lines). (C) 1995 by The American Society of Hematology.